Despite advances in the ability to detect and treat breast cancer, it remains a leading cause of death in women with cancer, and the incidence is rising (Siegel et al. (2013) CA Cancer J. Clin. 63:11-30). Approximately 15-20% of all cases are classified as triple-negative breast cancer, a subtype that is frequently associated with rapid progression and poor outcomes (Siegel et al. (2013) CA Cancer J Clin. 63:11-30; Lee et al. (2010) Cancer Biol. Ther. 9:1017-1024). Triple-negative breast cancer refers to the lack of detectable markers for the estrogen receptor (ER), progesterone receptor (PR), and Her2/neu amplification.
Treatment of patients with triple-negative breast cancer has been challenging due to the heterogeneity of the disease and the absence of well-defined molecular targets (Pegram et al. (1998) J. Clin. Oncol. 16:2659-2671; Wiggans et al. (1979) Cancer Chemother. Pharmacol. 3:45-48; Carey et al. (2007) Clin. Cancer Res. 13:2329-2334). Triple-negative breast cancer tumors are generally larger in size, are of higher grade, have lymph node involvement at diagnosis, and are biologically more aggressive than other types of breast cancer tumors (Haffty (2006) J. Clin. Oncol. 24:5652-5657). Despite having higher rates of clinical response to presurgical (neoadjuvant) chemotherapy, triple-negative breast cancer patients have a higher rate of distant recurrence and a poorer prognosis than women with other breast cancer subtypes (Haffty (2006) J. Clin. Oncol. 24:5652-5657; Dent et al. (2007) Clin. Cancer Res. 13:4429-4434). These tumors do not respond to the most effective and least toxic therapies, including hormonal therapy (tamoxifen) or herceptin. Less than 30% of women with metastatic triple-negative breast cancer survive 5 years, and almost all die of their disease despite adjuvant chemotherapy, which is the mainstay of treatment (Dent et al. (2007) Clin. Cancer Res. 13:4429-4434).